Am J Med Genet A

. 2020 Sep 21. doi: 10.1002/ajmg.a.61878. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/32954677/

Congenital diaphragmatic hernia as a prominent feature of a SPECC1L-related syndrome

K Taylor Wild ^1 2, Tia Gordon ^3 4, Elizabeth J Bhoj ^1 5, Haowei Du ³, Shalini N Jhangiani ⁶, Jennifer E Posey ³, James R Lupski ^3 6 7 8, Daryl A Scott ^3 8 9, Elaine H Zackai ¹Affiliations expand

• PMID: 32954677
• DOI: 10.1002/ajmg.a.61878

Abstract

Congenital diaphragmatic hernias (CDH) confer substantial morbidity and mortality. Genetic defects, including chromosomal anomalies, copy number variants, and sequence variants are identified in ~30% of patients with CDH. A genetic etiology is not yet found in 70% of patients, however there is a growing number of genetic syndromes and single gene disorders associated with CDH. While there have been two reported individuals with X-linked Opitz G/BBB syndrome with MID1 mutations who have CDH as an associated feature, CDH appears to be a much more prominent feature of a SPECC1L-related autosomal dominant Opitz G/BBB syndrome. Features unique to autosomal dominant Opitz G/BBB syndrome include branchial fistulae, omphalocele, and a bicornuate uterus. Here we present one new individual and five previously reported individuals with CDH found to have SPECC1L mutations. These cases provide strong evidence that SPECC1L is a bona fide CDH gene. We conclude that a SPECC1L-related Opitz G/BBB syndrome should be considered in any patient with CDH who has additional features of hypertelorism, a prominent forehead, a broad nasal bridge, anteverted nares, cleft lip/palate, branchial fistulae, omphalocele, and/or bicornuate uterus.

Keywords: MID1; Opitz G/BBB syndrome; SPECC1L-related syndrome; congenital diaphragmatic hernia (CDH).

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